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The role of immune cells and mediators in preeclampsia

Nature Reviews Nephrology volume 19, pages 257–270 (2023)Cite this article

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Abstract

Preeclampsia is a hypertensive disorder of major concern in pregnancy than can lead to intrauterine growth restriction, placental abruption and stillbirth. The pathophysiology of preeclampsia is multifactorial, including not only kidney dysfunction but also endothelial dysfunction, as the maternal endothelium becomes exposed to placental factors that are released into the circulation and increase systemic levels of vasoconstrictors, oxidative stress, anti-angiogenic factors and inflammatory mediators. Importantly, inflammation can lead to insufficient placental perfusion and low birthweight in offspring. Various innate and adaptive immune cells and mediators have been implicated in the development of preeclampsia, in which oxidative stress is associated with activation of the maternal inflammatory response. Immune cells such as regulatory T cells, macrophages, natural killer cells, and neutrophils are known to have major causative roles in the pathology of preeclampsia, but the contributions of additional immune cells such as B cells, inflammatory cytokines and anti-angiotensin II type 1 receptor autoantibodies are also now recognized. Immunological interventions, therefore, have therapeutic potential in this disease. Here, we provide an overview of the immune responses that are involved in the pathogenesis of preeclampsia, including the role of innate and adaptive immune cells and mediators.

Key points

  • Endothelial dysfunction, angiogenesis, spiral uterine artery remodelling and inadequate trophoblast invasion are key contributors to the genesis of hypertensive disorders during pregnancy.

  • An altered immune response might have a pivotal role in the development of preeclampsia, eclampsia and haemolysis, elevated liver enzymes and low platelets syndrome.

  • Insufficient or inadequate regulation of the immune system, activation of innate immune cells and imbalanced differentiation of T helper cell subsets create a cytotoxic environment that results in oxidative stress, endothelial dysfunction and intrauterine growth restriction.

  • T helper cells facilitate the activation of B cells that secrete anti-angiotensin II type 1 receptor autoantibodies, which can cause hypertension, cerebral dysfunction, kidney dysfunction and intrauterine growth restriction in response to placental ischaemia.

  • New therapeutics that target the pro-inflammatory response during preeclampsia have potential to attenuate the effects of the systemic factors that promote the development of this hypertensive disorder of pregnancy.

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Fig. 1: Pathophysiology of hypertensive disorders during pregnancy.
Fig. 2: Mechanisms of endothelial dysfunction in preeclampsia.
Fig. 3: Mitochondrial dysfunction and the pathogenesis of preeclampsia.
Fig. 4: Immune alterations in preeclampsia.
Fig. 5: The roles of T and B cells in preeclampsia.

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Authors and Affiliations

  1. Department of Pharmacology & Toxicology, University of Mississippi Medical Center, Jackson, MS, USA

    Evangeline Deer, Owen Herrock, Nathan Campbell, Sarah Fitzgerald, Lorena M. Amaral & Babbette LaMarca

  2. Emergency Medicine, University of Mississippi Medical Center, Jackson, MS, USA

    Denise Cornelius

  3. Department of Obstetrics and Gynecology, University of Mississippi Medical Center, Jackson, MS, USA

    Babbette LaMarca

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All authors researched data for the article and wrote the manuscript. E.D. and B.L. made substantial contributions to discussions of the content, and reviewed or edited the manuscript before submission.

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Glossary

Fetal resorption

The disintegration and absorption of one or more fetuses in the uterus after the completion of organogenesis.

Flow-mediated dilation

A vascular function test traditionally performed in the brachial artery, which measures the change in artery diameter in response to reactive hyperaemia.

Hofbauer cells

A diverse population of fetal macrophages that reside within placental tissue (in the chorionic villus); they are present as early as 18 days post-conception and persist throughout pregnancy.

Spiral uterine artery remodelling

An adaptive process in pregnancy that allows placental blood flow volume to increase while blood flow resistance decreases.

Syncytiotrophoblasts

A specialized, continuous layer of epithelial cells that cover the surface of embryonic placental villi and are in direct contact with maternal blood.

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Deer, E., Herrock, O., Campbell, N. et al. The role of immune cells and mediators in preeclampsia. Nat Rev Nephrol 19, 257–270 (2023). https://doi.org/10.1038/s41581-022-00670-0

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